Antimicrobials V2 Flashcards
Penicillin G is administed
IM or IV
Penicillin V is administed
orally
mechanism of penicillins
covalent binding to transpeptidases/PBPs, cross-linking, activation of autolysins
penicillins are bacterio-
cidal
block penicillin excretion with
probenecid
most ICWS inhibitors exibit
time dependent cell killing
clinical use: Pen G and Pen V
gram +
clinical use: anti-staphylococcal penicillins
beta-lactamase resistant
HHEELPSS
H. flu, H. pylori, E. coli, Enterococci, Listeria, Proteus mirabilis, Salmonella, Shigella
anti-staphylococcal penicillins
nafcillin, methicillin, isooxazolyl
extended spectrum antibiotics
ampicillin, amoxacillin
clinical use: extended spectrum penicillins
increased gram - activity
anti-pseudomonal penicillins
ticarcillin, piperacillin, mezlocillin
clinical use: anti-pseudomonal penicillins
effective against psuedomonas and some other gram -
due to rapid emergence of resistance with pseudomonas, use anti-psuedomonal penicillins in combination with
aminoglycosides or fluoroquinolones
adverse effects of penicillins
ampicillin rash
hypersensitivity: complete cross-linking
seizures w/ renal failure
resistance to penicillins
inaccessible PBPs (MRSA or gram -)
B-lactamase production
to reduced beta lactamase activity, administer penicillins with
b lactamase inhibitors
b lactamase inhibitors
clavulanic acid (augmenin)
sulbactam
tazobactam
clavulanic acid….
dramatically increases effects of pens
mechanism of cephalosporins
b-lactams, similar to pens
pen-sensitive patients may have cross reactivity with
cephalosporins
cephalosporins are bacterio
cidal
1st gen cephalosporins
cefazolin
cephalexin
2nd gen cephalosporins
cefuroxime
cefotetan
cefactor
3rd gen cephalosporins
ceftriaxone
cefotaxime
ceftazidime
cefpdoxime
4th gen cephalosporins
cefepime
cefepime exhibits _______ resistance
cephalosporinase
clinical use: 1st gen cephalosporins
gram +
clinical use: 2nd gen cephalosporins
some gram -, less gram +
clinical use: 3rd gen cephalosporins
serious gram - resistant to other b-lactams
clinical use: 4th gen cephalosporins
pseudomonas and cephalosporinase resistance
adverse effects: cephalosporins
irritation from injection
renal toxicity- enhanced by aminoglycosides
hypersensitivity
vitamin K deficiency
what antibiotics gives the Disulfiram effect?
cefotetan, bleeding and platelet disorders
what antibiotics gives the Disulfiram effect?
cefotetan, bleeding and platelet disorders
mechanism: azteronam
b lactam
clinical use: aztreonam
psuedomonas B-lactamase resistant
can azteronam cross the blood brain barrier?
yes
do azteronam exibit cross reactivity in pen-sensitive patients?
no
mechanism: imipenem
b lactam
clinical use: imipenem
broad, gram + and -
can imipenem cross the blood brain barrier?
yes
administration: imipenem
IV only
what should you coadminister with Imipenem?
cilastatin
inactivated by renal peptidase
meropenem
dipeptidase resistant carbapenem
does imipenem exhibit cross reactivity with pen-sensitive patients?
yes but incidence is low
mechanism: vancomycin
inhibits transglycosylation
vancomycin is bacteri-
cidal for gram +
vancomycin works synergistically with
aminoglycosides
vancomycin is given IV for
systemic use
vancomycin is given orally for
C. diff
clinical use: vancomycin
MRSA
adverse effects: vancomycin
flushing syndrome
renal and oto toxicity esp w/ aminoglycosides
mechanism: fosfomycin
inhibits cytoplasmic step in cell wall precursor synthesis
inhibits MurA blocking PG synthesis
clinical use: fosfomycin
gram + and gram -
single dose therapy UTI
fosfomycin is synergistic with
b lactams
aminoglycosides
fluoroquinolones
adverse effect: bacitracin
nephrotoxic
administration: bacitracin
topical only
pharmacokinetics: fosfomycin
G6P transporter
mechanism: colistin
act as detergents
clinical use: colistin
gram -
administation: colistin
topical due to renal toxicity
colistin is used as salvage therapy for
acinetobacter, pseudomonas, enterobacterieae
mechanism: tetracycline
reversible binding to 30S subunit
tetracycline is bacterio-
static
what class chelate metal ions?
tetracycline
what class should not be administered with calcium products?
tetracycline
can tetracyclines cross the placenta?
yes
excretion of doxycline
fecal
excretion of most tetracycline
urine
clinical use: tetracycline
broad spectrum
mycoplasma, chlamydia, rickettsiae
lyme disease
adverse effects: tetracycline
GI irritation
superinfections
liver damage
photosensitization
calcium chelation
resistance to tetracyclines
mainly efflux pumps
altered ribosomal proteins
glycycycline
newest tetracycline
retain antibacterial spectrum but overcome resistance
tigecycline is
not effected by efflux pump
tigecycline comes with
FDA black box warning, very dangerous
macrolides
erythromycin, clarithromycin, azithromycin
do macrolides distribute to CNS?
no
can macrolides cross the placenta?
yes
excretion: macrolides
bile
administration: macrolides
oral and IV
clinical use: macrolides
gram +, some gram -
mycoplasma pneumoniae, legionnaire’s, chlamydia
can macrolides be given to pen-sensitive patients?
yes
broad spectrum macrolides
azithromycin and clarithromycin
adverse effects: macrolides
GI distress
microsomal enzyme inhibition
hepatotoxicity
QT prolongation
resistance: macrolides
staph resistant
methylated rRNA
efflux pump
esterase
benefits of clarithromycin
less GI effects
longer half life
which macrolide has minimal P450 interactions?
azithromycin
clarithromycin and azithromycin have
better bioavailability
active against mycobacterium avium
mechanism: telithromycin
binds 50S subunit
pharmacokinetics: telithromycin
poor substrate for efflux
inhibits CYP3A4
excretion: telithromycin
bile and urine
clinical use: telithromycin
RTIs
adverse effects: telithromycin
PQ prolongation
mechanism: aminoglycosides
irreversible inactivation of 30S
administration: aminoglycosides
usually IV
where do aminoglycosides NOT distribute?
eye, CNS
aminoglycosides and fluoroquinolones exhibit
concentration dependent killing
clinical uses: aminoglycosides
gram -
aminoglycosides for psuedomonas
gentamycin –> tobramycin –> amikacin
**oldest to newest
older aminoglycosides
streptomycin, gentamycin
adverse effects: aminoglycosides
nephrotoxicity
ototoxicity
dose and time dependent
resistance: aminoglycosides
evolves rapidly if AG is used alone
increased bacterial metabolism
alteration in bacterial uptake
altered ribosomal target
mechanism: chloramphenicol
reversible inhibitor of protein synthesis
chloramphenicol is bacterio
static
does chloarmphenicol distribute to the CNS?
yes
excretion: chloramphenicol
urine
resistance: chloramphenicol
plasmid mediated
CAT
slow development
adverse effects: chloramphenicol
GI upset
anemia due to bone marrow depression
aplastic anemia (Irreversible and fatal)
Gray baby syndrome
inhibits CYP450
clindamycin is bacterio
static
mechanism: clindamycin
binds 50S subunit
does clindamycin distribute to the CNS?
no
clinical use: clindamycin
MRSA, endocarditis prophylaxis
adverse effects: clindamycin
GI upset, C. diff, superinfections, hepatotoxicity
streptogramins
quinupristin, dalfopristin
mechanism: streptogramins
peptide macrolactones- bind novel ribosomal subunits
administation: streptogramins
IV
excretion: streptogramins
mostly bile, some urine
streptogramins inhibit
CYP34A
clinical use: streptogramins
vancomycin and MDR MRSA
resistance: streptogramins
complete cross resistance between the two components
mechanism: linezolid
prevents formation of 70S ribosome
administration: linezolid
IV or oral
clinical use: linezolid
bactericidal against streptococci
bacteriostatic against staphylococci and enterococci
vancomycin resistant e. faecium
limited to MDR gram+
adverse effects: linezolid
bone marrow suppression, thrombocytopenia
mechanism: sulfonamides
inhibit folate synthesis, PABA analogs
sulfonamides are bacterio
static
administration: sulfonamides
oral
are sulfonamides distributed to the CNS?
yes
excretion: sulfonamides
urine
topical sulfonamide for burns
silver sulfadizine
sulfonamide for ulcerative colitis
sulfasalazine
sulfonamide for ulcerative colitis
sulfasalazine
combine sulfonamides with
trimethoprim
adverse effects: sulfonamides
allergic reactions
cross reaction with other sulfonamides
Stevens Johnson syndrome
hematuria
resistance: sulfonamides
too much PABA
loss of permeability
new form of dihydropteroate synthesis
mechanism: trimethoprim
block bacterial enzyme that converts dihydrofolate reductase to tetrahydrofolate
adverse effects: trimethoprim
megaloblastic anemia
leukopenia
granulocytopenia
co-trimoxazole
add typical sulfonamide effectds
AIDS patients treat for pneumocystits receiving co-trimoxazole have
higher incidence of adverse effects
mechanism: Fluoroquinolones
DNA gyrase inhibitors
topo II and topo IV
fluoroquinolones
ciprofloxacin, levofloxacin
fluoroquinolones excretion is blocked by
probenecid
clinical use: fluoroquinolones
gram -, esp GI and UTI
adverse effects: fluoroquinolones
GI upset
connective tissue disorder
headaches, dizziness, insomnia
abnormal LFTs
resistance: fluoroquinolones
mutated DNA gyrase
plasmid-mediated protection
decreased permeability
Nitrofurantoin
UTIs
no systemic effect, excreted in urine
adverse effects: nitrofurantoin
anorexia
GI upset
hemolytic anemia
resistance: nitrofurantoin
psuedomonas
isoniazid mechanism
blocks synthesis of mycolic acid cell wall
can isoniazid distribute to the CNS?
yes
isoniazid metabolism
slow acetylators
clinical use: isoniazid
prophylaxis: TB
combination therapy for TB with IPE
adverse effects: isoniazid
dose and duration dependent
hepatotoxicity
peripheral and central neuropathy (B6)
resistance: isoniazid
mutation of KatG gene
mechanism: rifampin
inhibits DNA dependent RNA polymerase
rifampin is bacterio
cidal
excretion: rifampin
bile
adverse effects: rifampin
induced of microsomal enzymes
hepatotoxic
flu-like syndrome
mechanism: ethambutol
inhibits synthesis of mycobacterial and cell wall glycan via blocking arabinosyltransferase
is ethambutol distributed to CNS?
yes
excretion: ethambutol
urine
adverse effects: ethambutol
dose dependent
optic neuritis, color blindess
resistance: ethambutol
rapid, use in combination
pyrazinamide is bacterio
static
mechanism: pyrazinamide
activated by mycobacterium, blocks membrane functions
resistance: pyrazinamide
rapid, use in combination
adverse effects: pyrazinamide
hyperuricemia-gout
hepatotoxicity
contraindicated in pregnancy
second line TB drugs
extreme cases
PAS, cycloserine, ethionamide
dapsone
leprosy, p. jirovecii
hepatotoxicity ICE T
Isoniazid
Clindamycin
Erythromycin
Tetracycline
Ototoxicity: VA
vancomycin
aminoglycosides
renal toxicity: CAVS
Cavities in Kidneys
cephalosporins
aminoglycosides
vancomycin
sulfonamides
DOC H. flu
3rd gen cephalosporin
DOC rickettsia/lyme disease
doxycycline
DOC legionella
erythromycin, macrolides
DOC m. tuberculosis
RIPE
DOC M. pneumoniae
macrolides
DOC C. diff
vancomycin
pneumonia outpatient therapy healthy adults without risk
doxycycline, amoxicillin
***macrolide monotherapy (z pack) no longer recommended for S. pneumoniae
pneumonia outpatient therapy adults with risk factors
amoxicillin/clavulanate OR
cephalosporin AND macrolide or doxycycline OR
fluoroquinolone alone
pneumonia inpatient therapy no risk factors
ampicillin sulbactam OR
cephalosporin and macrolide OR
fluroquinolone alone
pneumonia inpatient therapy, no risk factor BUT contraindication to macrolides and fluoroquinolones
beta lactam OR cephalosporin
AND doxycycline
pneumonia inpatient therapy, risk for MRSA
vancomycin, linezolid
pneumonia inpatient therapy, risk for Psuedomonas
piperacillin tazobactam
cefepime or carbapenems